uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Fluorescence imaging of macromolecule transport in high molecular weight cut-off microdialysis
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Microsystems Technology.
2014 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 406, no 29, 7601-7609 p.Article in journal (Refereed) Published
Abstract [en]

When microdialysis (MD) membrane exceeds molecular weight cut-off (MWCO) of 100 kDa, the fluid mechanics are in the ultrafiltration regime. Consequently, fluidic mass transport of macromolecules in the perfusate over the membrane may reduce the biological relevance of the sampling and cause an inflammatory response in the test subject. Therefore, a method to investigate the molecular transport of high MWCO MD is presented. An in vitro test chamber was fabricated to facilitate the fluorescent imaging of the MD sampling process, using fluoresceinylisothiocyanate (FITC) dextran and fluorescence microscopy. Qualitative studies on dextran behavior inside and outside the membrane were performed. Semiquantitative results showed clear dextran leakage from both 40 and 250 kDa dextran when 100 kDa MWCO membranes were used. Dextran 40 kDa leaked out with an order of magnitude higher concentration and the leakage pattern resembled more of a convective flow pattern compared with dextran 250 kDa, where the leakage pattern was more diffusion based. No leakage was observed when dextran 500 kDa was used as a colloid osmotic agent. The results in this study suggest that fluorescence imaging could be used as a method for qualitative and semiquantitative molecular transport and fluid dynamics studies of MD membranes and other hollow fiber catheter membranes.

Place, publisher, year, edition, pages
2014. Vol. 406, no 29, 7601-7609 p.
National Category
Other Medical Engineering Engineering and Technology
Identifiers
URN: urn:nbn:se:uu:diva-239233DOI: 10.1007/s00216-014-8192-yISI: 000344860300019PubMedID: 25286875OAI: oai:DiVA.org:uu-239233DiVA: diva2:773845
Available from: 2014-12-19 Created: 2014-12-19 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Microdialysis Sampling of Macro Molecules: Fluid Characteristics, Extraction Efficiency and Enhanced Performance
Open this publication in new window or tab >>Microdialysis Sampling of Macro Molecules: Fluid Characteristics, Extraction Efficiency and Enhanced Performance
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this thesis, fluid characteristics and sampling efficiency of high molecular weight cut-off microdialysis are presented, with the aim of improving the understanding of microdialysis sampling mechanisms and its performance regarding extraction efficiency of biological fluid and biomarkers.

Microdialysis is a well-established clinical sampling tool for monitoring small biomarkers such as lactate and glucose. In recent years, interest has raised in using high molecular weight cut-off microdialysis to sample macro molecules such as neuropeptides, cytokines and proteins. However, with the increase of the membrane pore size, high molecular weight cut-off microdialysis exhibits drawbacks such like unstable catheter performance, imbalanced fluid recovery, low and unstable molecule extraction efficiency, etc. But still, the fluid characteristics of high molecular weight cut-off microdialysis is rarely studied, and the clinical or in vitro molecule sampling efficiency from recent studies vary from each other and are difficult to compare.  

Therefore, in this thesis three aspects of high molecular weight cut-off microdialysis have been explored. The first, the fluid characteristics of large pore microdialysis has been investigated, theoretically and experimentally. The results suggest that the experimental fluid recovery is in consistency with its theoretical formula. The second, the macromolecule transport behaviour has been visualized and semi-quantified, using an in vitro test system and fluorescence imaging. The third, two in vitro tests have been done to mimic in vivo cerebrospinal fluid sampling under pressurization, using native and differently surface modified catheters. As results, individual protein/peptide extraction efficiencies were achieved, using targeted mass spectrometry analysis.

In summary, a theory system of the fluid characteristics of high molecular weight cut-off microdialysis has been built and testified; Macromolecular transport of microdialysis catheter has been visualized; In vivo biomolecules sampling has been simulated by well-defined in vitro studies; Individual biomolecular extraction efficiency has been shown; Different surface modifications of microdialysis catheter have been investigated. It was found that, improved sampling performance can be achieved, in terms of balanced fluid recovery and controlled protein extraction efficiency.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 52 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1278
Keyword
microdialysis, high molecular weight cut-off, fluid characteristics, fluid recovery, extraction efficiency, biomarker, microporous membrane, macromolecule transport, transmembrane, large pore, surface modification, pluronic, dextran, in vitro, microdialysis catheter
National Category
Manufacturing, Surface and Joining Technology Nano Technology
Research subject
Engineering Science with specialization in Microsystems Technology; Engineering Science with specialization in Materials Science
Identifiers
urn:nbn:se:uu:diva-261068 (URN)978-91-554-9315-8 (ISBN)
Public defence
2015-10-16, Polhem Salen, Angstrom Laboratory, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Berzelii Centre EXSELENT
Available from: 2015-09-25 Created: 2015-08-28 Last updated: 2015-10-01

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Authority records BETA

Chu, JiangtaoHjort, KlasDahlin, Andreas P

Search in DiVA

By author/editor
Chu, JiangtaoHjort, KlasDahlin, Andreas P
By organisation
Microsystems Technology
In the same journal
Analytical and Bioanalytical Chemistry
Other Medical EngineeringEngineering and Technology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 913 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf